Mitochondrial transplantation preserves myocardial function and viability in pediatric and neonatal pig hearts donated after circulatory death

被引:10
作者
Alemany, Victor S. [1 ]
Nomoto, Rio [1 ]
Saeed, Mossab Y. [1 ]
Celik, Aybuke [1 ]
Regan, William L. [1 ]
Matte, Gregory S. [1 ]
Recco, Dominic P. [1 ]
Emani, Sitaram M. [1 ,2 ]
del Nido, Pedro J. [1 ]
McCully, James D. [1 ,2 ]
机构
[1] Boston Childrens Hosp, Dept Cardiac Surg, 300 Longwood Ave, Boston, MA 02115 USA
[2] Harvard Med Sch, Boston, MA USA
关键词
donation after circulatory death; heart trans-plant; ischemia; mitochondrial transplantation; neonatal; pediatric; REPERFUSION; ISCHEMIA; CARDIOPROTECTION; PROTECTION; STRATEGY;
D O I
10.1016/j.jtcvs.2023.05.010
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Mitochondrial transplantation has been shown to preserve myocardial function and viability in adult porcine hearts donated after circulatory death (DCD) . Herein, we investigate the efficacy of mitochondrial transplantation for the preser-vation of myocardial function and viability in neonatal and pediatric porcine DCD heart donation.Methods: Circulatory death was induced in neonatal and pediatric Yorkshire pigs by cessation of mechanical ventilation. Hearts underwent 20 or 36 minutes of warm ischemia time (WIT), 10 minutes of cold cardioplegic arrest, and then were harvested for ex situ heart perfusion (ESHP). Following 15 minutes of ESHP, hearts received either vehicle (VEH) or vehicle containing isolated autologous mitochon-dria (MITO). A sham nonischemic group (SHAM) did not undergo WIT, mimicking donation after brain death heart procurement. Hearts underwent 2 hours each of unloaded and loaded ESHP perfusion.Results: Following 4 hours of ESHP perfusion, left ventricle developed pressure, dP/ dt max, and fractional shortening were significantly decreased (P < .001) in DCD hearts receiving VEH compared with SHAM hearts. In contrast, DCD hearts receiving MITO exhibited significantly preserved left ventricle developed pressure, dP/dt max, and fractional shortening (P < .001 each vs VEH, not significant vs SHAM). Infarct size was significantly decreased in DCD hearts receiving MITO as compared with VEH (P < .001). Pediatric DCD hearts subjected to extended WIT demonstrated significantly preserved fractional shortening and significantly decreased infarct size with MITO (P < .01 each vs VEH).Conclusions: Mitochondrial transplantation in neonatal and pediatric pig DCD heart donation significantly enhances the preservation of myocardial function and viability and mitigates against damage secondary to extended WIT. (J Thorac Cardiovasc Surg 2024;167:e6-21)
引用
收藏
页码:e6 / e21
页数:16
相关论文
共 34 条
[1]  
BARNARD C N, 1967, South African Medical Journal, V41, P1271
[2]   Delayed Transplantation of Autologous Mitochondria for Cardioprotection in a Porcine Model [J].
Blitzer, David ;
Guariento, Alvise ;
Doulamis, Ilias P. ;
Shin, Borami ;
Moskowitzova, Kamila ;
Barbieri, Giovanna Ramirez ;
Orfany, Arzoo ;
del Nido, Pedro J. ;
McCully, James D. .
ANNALS OF THORACIC SURGERY, 2020, 109 (03) :711-719
[3]   Outcomes of Donation After Circulatory Death Heart Transplantation in Australia [J].
Chew, Hong Chee ;
Iyer, Arjun ;
Connellan, Mark ;
Scheuer, Sarah ;
Villanueva, Jeanette ;
Gao, Ling ;
Hicks, Mark ;
Harkness, Michelle ;
Soto, Claudio ;
Dinale, Andrew ;
Nair, Priya ;
Watson, Alasdair ;
Granger, Emily ;
Jansz, Paul ;
Muthiah, Kavitha ;
Jabbour, Andrew ;
Kotlyar, Eugene ;
Keogh, Anne ;
Hayward, Chris ;
Graham, Robert ;
Spratt, Phillip ;
Macdonald, Peter ;
Dhital, Kumud .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2019, 73 (12) :1447-1459
[4]   Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection [J].
Cowan, Douglas B. ;
Yao, Rouan ;
Akurathi, Vamsidhar ;
Snay, Erin R. ;
Thedsanamoorthy, Jerusha K. ;
Zurakowski, David ;
Ericsson, Maria ;
Friehs, Ingeborg ;
Wu, Yaotang ;
Levitsky, Sidney ;
del Nido, Pedro J. ;
Packard, Alan B. ;
McCully, James D. .
PLOS ONE, 2016, 11 (08)
[5]   DCD donations and outcomes of heart transplantation: the Australian experience [J].
Dhital, Kumud ;
Ludhani, Prakash ;
Scheuer, Sarah ;
Connellan, Mark ;
Macdonald, Peter .
INDIAN JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2020, 36 (SUPPL 2) :224-232
[6]   Mitochondrial transplantation for myocardial protection in diabetic hearts [J].
Doulamis, Ilias P. ;
Guariento, Alvise ;
Duignan, Thomas ;
Orfany, Arzoo ;
Kido, Takashi ;
Zurakowski, David ;
Del Nido, Pedro J. ;
McCully, James D. .
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, 2020, 57 (05) :836-845
[7]  
Duignan Thomas, 2020, J Extra Corpor Technol, V52, P303, DOI 10.1182/ject-2000034
[8]   Potential for donation after circulatory death heart transplantation in the United States: Retrospective analysis of a limited UNOS dataset [J].
Farr, Maryjane ;
Truby, Lauren K. ;
Lindower, Joel ;
Jorde, Ulrich ;
Taylor, Samantha ;
Chen, Leway ;
Gass, Alan ;
Stevens, Gerin ;
Reyentovich, Alex ;
Mancini, Donna ;
Arcasoy, Selim ;
Delair, Samantha ;
Pinney, Sean .
AMERICAN JOURNAL OF TRANSPLANTATION, 2020, 20 (02) :525-529
[9]   Mitochondrial transplantation for myocardial protection in ex-situ-perfused hearts donated after circulatory death [J].
Guariento, Alvise ;
Doulamis, Ilias P. ;
Duignan, Thomas ;
Kido, Takashi ;
Regan, William L. ;
Saeed, Mossab Y. ;
Hoganson, David M. ;
Emani, Sitaram M. ;
Fynn-Thompson, Francis ;
Matte, Gregory S. ;
Nido, Pedro J. del ;
McCully, James D. .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2020, 39 (11) :1279-1288
[10]   Preischemic autologous mitochondrial transplantation by intracoronary injection for myocardial protection [J].
Guariento, Alvise ;
Blitzer, David ;
Doulamis, Ilias ;
Shin, Borami ;
Moskowitzova, Kamila ;
Orfany, Arzoo ;
Ramirez-Barbieri, Giovanna ;
Staffa, Steven J. ;
Zurakowski, David ;
del Nido, Pedro J. ;
McCully, James D. .
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2020, 160 (02) :E15-E29